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Abstract
Aim The DR2 supertype currently comprises 204 DRB1∗15 and 65 DRB1∗16 alleles. With few exceptions, DR2 alleles associate with one of 46 DRB5 alleles. DRB5-DRB1-DQA1-DQB1 haplotypes may differ among diverse world populations. We used NGS for HLA genotyping of commercial human population panels composed primarily of unrelated individuals. We report here on the 170 DR2 alleles and haplotypes identified among 541 individuals in 6 sample panels. Methods The sample panels were from the Coriell repository: hapmappt02, hapmappt04, hapmappt05, hapmappt06, MGP00010 and MGP00019. Hapmappt06 represents CEPH family pairs and trios. NGS genotyping of HLA-A, B, C, DRB5, DRB1, DQA1, DQB1, DPA1, DPB1 employed an amplicon based technology assessing all exons with intervening intron data to exclude known null alleles. DRB5-DRB1-DQA1-DQB1 haplotypes were inferred based on common associations in publically available data sets: bioinformatics.bethematchclinical.org and the IMGT HLA database. Results Three DRB1∗15 alleles, two DRB1∗16 and three DRB5 alleles were identified on 12 different haplotypes, see Table. DRB1∗15:01:01 was found in 6 associations. Most frequent was DRB5∗0101:01-DRB1∗15:01:01-DQA1∗01:02:01-DQB1∗06:02:01, found in all panels except Gambian. DRB1∗15:02:01, almost exclusive to Asians, was found in 2 linkages, with DRB5∗01:02-DRB1∗15:02:01-DQA1∗01:03:01-DQB1∗06:01:01 most frequent. DRB1∗15:03:01, on DRB5∗01:01:01-DRB1∗15:03:01-DQA1∗01:02:01-DQB1∗06:02:01, was found only in Nigerian. DRB1∗16:01:01, only in Caucasian, associated with DRB5∗02:02-DQA1∗01:02:02-DQB1∗05:02:01. DRB1∗16:02:01, seen in Asian and Gambian, was found most frequently with DRB5∗02:02-DQA1∗01:02:02-DQB1∗05:02:01, but also with DRB5∗01:01:01-DQA1∗01:02:02-DQB1∗05:02:01. Conclusions Seven DR2 haplotypes appear to be the results of historic recombination events. DR2 alleles and haplotypes are diverse and differ among human populations. Download : Download high-res image (718KB) Download : Download full-size image
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